Rathje Kristin, Gagelmann Nico, Badbaran Anita, Langebrake Claudia, Dadkhah Adrin, Richter Johanna, Massoud Radwan, Schäfersküpper Mathias, Marquard Franziska E, Oechsler Sofia, Klyuchnikov Evgeny, Rudolph Ina, Heidenreich Silke, Niederwieser Christian, Lueck Catherina, Janson Dietlinde, Wolschke Christine, Fehse Boris, Ayuk Francis, Kröger Nicolaus
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hospital Pharmacy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Am J Hematol. 2025 Feb;100(2):200-209. doi: 10.1002/ajh.27529. Epub 2024 Nov 16.
Despite the introduction of JAK inhibitors, allogeneic hematopoietic cell transplant remains the only potentially curative treatment for patients with myelofibrosis but has considerable treatment-related complications. Whether the incorporation of JAK inhibition into the transplant algorithm leads to improved outcomes is still unclear. Here, we analyzed different transplant platforms in myelofibrosis patients undergoing a first transplant, comparing immune profiles and outcomes of (1) 33 patients continuing JAK inhibition at start of conditioning until stable engraftment (PERI-group), (2) 38 patients receiving JAK inhibition prior to transplant until start of conditioning (PRE-group), and (3) 38 patients that had never received JAK inhibition (NON-group). Patients in the PERI-group showed significantly higher early B-cell recovery as well as significantly increased late recovery of gamma-delta T cells and NK cells. We observed excellent neutrophil and platelet engraftment (100% for both) in the PERI-group and no hematotoxic effects or increased rates of infections following peri-transplant JAK inhibition. Cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV at day 100 after transplant was 15% in the PERI-group versus 29% in the PRE-group versus 34% in the NON-group. Cumulative incidence of relapse at 1 year after transplant was 9% in the PERI-group compared with 16% in the PRE-group and 18% in the NON-group. In conclusion, peri-transplant JAK inhibition was feasible with promising engraftment and acute GvHD rates, though deserves further investigation.
尽管已引入JAK抑制剂，但异基因造血细胞移植仍是骨髓纤维化患者唯一可能治愈的治疗方法，但存在相当多与治疗相关的并发症。将JAK抑制纳入移植方案是否能改善治疗结果仍不清楚。在此，我们分析了首次接受移植的骨髓纤维化患者的不同移植平台，比较了以下三组患者的免疫谱和治疗结果：（1）33例在预处理开始时持续使用JAK抑制剂直至稳定植入的患者（围移植期组）；（2）38例在移植前接受JAK抑制剂治疗直至预处理开始的患者（移植前组）；（3）38例从未接受过JAK抑制剂治疗的患者（未治疗组）。围移植期组患者早期B细胞恢复显著更高，γδT细胞和NK细胞的晚期恢复也显著增加。我们观察到围移植期组中性粒细胞和血小板植入情况良好（两者均为100%），围移植期JAK抑制后无血液毒性作用或感染率增加。移植后第100天急性移植物抗宿主病（GvHD）II-IV级的累积发生率在围移植期组为15%，移植前组为29%，未治疗组为34%。移植后1年复发的累积发生率在围移植期组为9%，移植前组为16%，未治疗组为18%。总之，围移植期JAK抑制是可行的，植入和急性GvHD发生率前景良好，尽管值得进一步研究。
